In silico Evaluation of the Inhibitory Potential of Cymbopogonol from Cymbopogon citratus Towards Falcipain-2 (FP2) Cysteine Protease of Plasmodium falciparum

Abstract

Antimicrobial resistance is a major challenge militating against the health of people globally. Plasmodium falciparum has developed resistance to current drugs used in tackling malaria, and this has remarkably contributed to an increased mortality rate in Sub-Saharan Africa. The inhibitory potential of cymbopogonol against Falcipain-2 (FP2) of the Plasmodium falciparum parasite was evaluated and achieved using a computational approach in this study. SwissADME, ADMETLab, and PROTOX-II servers were used to evaluate cymbopogonol's absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties in comparison to the other ligands. The test compound had a better docking score of -8.40 kcal/mol compared to the standard and co-crystallized ligand. The compound also had a hydrophobic interaction with LEU I:78, MET I:29, VAL I:44, VAL I:47, LEU I:25, and ARG I:43 present in the FP2 receptorbinding motif of the malaria parasite. The compound also possesses a favorable ADMET characteristics and demonstrated no tendency towards hERG inhibition, hepatotoxicity, carcinogenicity, mutagenicity, or drug-liver injury. Therefore, cymbopogonol may be used for experimental research and future medication development for the successful treatment of malaria.

Computational Drug Discovery for Novel Small Molecule Inhibitors Targeting LRRK2 in Parkinson's Disease Treatment

“…Heterocyclic compounds play an essential role in drug discovery and development, with considerable research dedicated to their synthesis and optimization (Tripathi et al, 2021;Babalola et al, 2021;Adetobi et al, 2022). These compounds, characterized by a ring structure containing atoms of at least two different elements, exhibit diverse pharmacological activities and are integral components of many clinically approved drugs.…”

“…(2018), a lead pharmacological agent should display a signi cant level of potency and good pharmacokinetic properties at a therapeutic dose. Due to the importance of ADMET in drug development, in silico models were developed to evaluate the pharmacokinetic properties of a potential lead before clinical experiment (Dong et al, 2018).Another signi cant physicochemical property that could in uence ADMET is lipophilicity and water solubility(Adetobi et al, 2022). Most oral compounds have higher lipophilicity value and logP value, implying that a germane relationship exist between these two (Diane et al, 2017).…”